Here, we show that intravenous (i.v.)or intranasal (i.n.)administration of apolipoprotein E peptide (ApoE)‐directed polymersome CpG nanoformulation (t‐NanoCpG) mediates efficient brain delivery of CpG, inducing strong immunotherapy of highly malignant murine LCPN glioma (Figure 1a). This evidence concerns the gene APOE and glioma.